Synthetic jet based medicament delivery method and apparatus

ABSTRACT

A dry powder inhaler consisting of first chamber having an orifice for holding a dry powder and a gas, and a second chamber for receiving a deaggregated form of the dry powder and for communicating the deaggregated dry powder to a user. A synthetic jet drives the dry powder from the first chamber to the second chamber.

CROSS REFERENCE TO RELATED APPLICATION

This application claims priority to co-pending U.S. ProvisionalApplication entitled “Synthetic Jet Based Medicament Delivery Method andApparatus”, having Ser. No. 60/547,323, Filed Feb. 24, 2004 which isentirely incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to the field of metering,packaging and delivery of pharmaceuticals and drugs. Particular utilityfor the present invention is found in delivery of metered and packageddry powder medications and drugs for inhalation therapy and will bedescribed in connection with such utility, although other utilities arecontemplated, including liquid medication applications.

DISCUSSION OF THE PRIOR ART

Certain diseases of the respiratory tract are known to respond totreatment by the direct application of therapeutic agents. As theseagents are most readily available in dry powdered form, theirapplication is most conveniently accomplished by inhaling the powderedmaterial through the nose or mouth. This powdered form results in thebetter utilization of the medication in that the drug is depositedexactly at the site desired and where its action may be required; hence,very minute doses of the drug are often equally as efficacious as largerdoses administered by other means, with a consequent marked reduction inthe incidence of undesired side effects and medication cost.Alternatively, the drug in powdered form may be used for treatment ofdiseases other than those of the respiratory system. When the drug isdeposited on the very large surface areas of the lungs, it may be veryrapidly absorbed into the blood stream; hence, this method ofapplication may take the place of administration by injection, tablet,or other conventional means.

It is the opinion of the pharmaceutical industry that thebioavailability of the drug is optimum when the drug particles deliveredto the respiratory tract are between 1 to 5 microns in size. When thedrug particles need to be in this size range the dry powder deliverysystem needs to address a number of issues:

(1) Small size particles develop an electrostatic charge on themselvesduring manufacturing and storage. This causes the particles toagglomerate or aggregate, resulting in clusters of particles which havean effective size greater than 5 microns. The probability of these largeclusters making it to the deep lungs then decreases. This in turnresults in a lower percentage of the drug being available to the patientfor absorption.

(2) The amount of active drug that needs to be delivered to the patientmay be of the order of tens of micrograms. Since current powder fillingequipment cannot effectively deliver aliquots of drugs in microgramquantities with acceptable accuracy, the standard practice is to mix theactive drug with a filler or bulking agent such as lactose. Thisadditive also makes the drug “easy to flow”. In some cases this filleris sometimes called a carrier. These carrier particles are often largerthan the drug particles in size. The ability of the dry powder inhalerto separate drug from the carrier is an important performance parameterin the effectiveness of the design.

(3) Active drug particles with sizes greater than 5 microns will bedeposited either in the mouth or throat. This introduces another levelof uncertainty since the bioavailability and absorption of the drug inthese locations is different from the lungs. Dry powder inhalers need tominimize the drug deposited in these locations to reduce the uncertaintyassociated with the bioavailability of the drug.

Prior art dry powder inhalers (DPIs) usually have a means forintroducing the drug (active drug plus carrier) into a high velocity airstream. The high velocity air-stream is used as the primary mechanismfor breaking up the cluster of micronized particles or separating thedrug particles from the carrier. Several inhalation devices useful fordispensing this powder form of medication are known in the prior art.For example, in U.S. Pat. Nos. 3,507,277; 3,518,992; 3,635,219;3,795,244; and 3,807,400, inhalation devices are disclosed having meansfor piercing or removing the top of a capsule containing a powderedmedication, which upon inhalation is drawn out of the pierced or toppedcapsule and into the user's mouth. Several of these patents disclosepropeller means, which upon inhalation aid in dispensing the powder outof the capsule, so that it is not necessary to rely solely on theinhaled air to suction powder from the capsule. For example, in U.S.Pat. No. 2,517,482, a device is disclosed having a powder containingcapsule placed in a lower chamber before inhalation, where it is piercedby manual depression of a piercing pin by the user. After piercing,inhalation is begun and the capsule is drawn into an upper chamber ofthe device where it moves about in all directions to cause a dispensingof powder through the pierced hole and into the inhaled air stream. U.S.Pat. No. 3,831,606 discloses an inhalation device having multiplepiercing pins, propeller means, and a self-contained power source foroperating the propeller means via external manual manipulation, so thatupon inhalation the propeller means aids in dispensing the powder intothe stream of inhaled air. See also U.S. Pat. No. 5,458,135.

These prior art devices present several problems and possess severaldisadvantages. For instance, these prior art devices require that theuser exert considerable effort in inhalation to effect dispensing orwithdrawal of powder from a pierced capsule into the inhaled air stream.With these prior art devices, suction of powder through the piercedholes in the capsule caused by inhalation generally does not withdrawall or even most of the powder out of the capsule, thus causing a wasteof the medication. Also, such prior art devices may result inuncontrolled amounts or clumps of powdered material being inhaled intothe user's mouth, rather than a constant inhalation of controlledamounts of finely dispersed powder.

The above description of the prior art is taken largely from U.S. Pat.No. 3,948,264 to Wilke et al, who disclose a device for facilitatinginhalation of a powdered medication that includes a body portion havingprimary and secondary air inlet channels and an outlet channel. Thesecondary inlet channel provides an enclosure for a capsule containingthe powdered medication, and the outlet channel is formed as amouthpiece protruding from the body. A capsule piercing structure isprovided, which upon activation forms one or more holes in the capsuleso that upon vibration of the capsule by an electromechanical vibrator,the powdered drug may be released from the capsule. The piercing meansdisclosed in Wilke et al includes three radially mounted, spring-biasedpiercing needles mounted in a trochoidal chamber. Upon hand rotation ofthe chamber, simultaneous inward radial motion of the needles piercesthe capsule. Further rotation of the chamber allows the needles to beretracted by their spring mountings to their original positions towithdraw the needles from the capsule. The electromechanical vibratorincludes, at its innermost end, a vibrating plunger rod which projectsinto the intersection of the inlet channel and the outlet channel.Connected to the plunger rod is a mechanical solenoid buzzer forenergizing the rod to vibrate. The buzzer is powered by a high energyelectric cell and is activated by an external button switch. Accordingto Wilke et al, upon inhalation through outlet channel 3 and concurrentpressing of switch 10 d to activate the electromechanical vibratingmeans 10, air is sucked through inlet channels 4 and 12 and the airstream through the secondary inlet channel 4 raises the capsule upagainst the vibrating plunger rod 10 a. The capsule is thus vibratedrapidly with powder being fluidized and dispensed from the pierced holestherein. (This technique is commonly used in manufacturing fordispensing powder through a hopper where the hopper is vibrated tofluidize the powder and move it through the hopper outlet. The piercedholes in the capsule represent the hopper outlet.) The air streamthrough inlet channel 4 and 12 aids in withdrawal of powder from thecapsule and carries this powder through the outlet channel 3 to themouth of the user. Wilke et al further discloses that theelectromechanical vibrator means may be placed at a right angle to theinlet chamber and that the amplitude and frequency of vibration may bealtered to regulate dispensing characteristics of the inhaler.

The prior art devices have a number of disadvantages which makes themless than desirable for the delivery of dry powder to the lungs. Some ofthese disadvantages are:

-   -   The performance of the prior art inhalers depends on the flow        rate generated by the user. Lower flow rate does not result in        the powder being totally deaggregated and hence adversely        affects the dose delivered to the patient.    -   Inconsistency in the bioavailability of the drugs from        dose-to-dose because of lack of consistency in the deaggregation        process.    -   Large energy requirements for driving the electromechanical        based inhalers which increases the size of the devices making        them unsuitable for portable use.    -   Loss of medication from opened or topped capsules.    -   Deterioration of medication in open or topped capsules due to        exposure to oxygen or moisture.

In my prior U.S. Pat. Nos. 6,026,809 and 6,142,146 (with Abrams), weprovide an inhaler that utilizes a vibrator to facilitate suspension ofa medication or drug into a gas that overcomes the aforesaid and otherdisadvantages and drawbacks of the above prior art. More particularly,the inhaler of my aforesaid patent includes a piezoelectric vibrator fordeaggregating the medication or drug and driving the deaggregatedmedication or drug into suspension. In one embodiment of the '809 patentdescribed in FIG. 3, inhaler 10 includes a hard plastic or metal housing18 having a generally L-shaped longitudinal cross-section. Housing 18includes four air flow openings 20, 28, 30, and 32. Inhaler 10 includesa main air flow passage 26 which extends the length of the housing 18from the front 22 (at opening 20) to the rear 24 thereof (at opening 28)and has a generally square-shaped transverse cross-section, so as topermit air flow therethrough (denoted by arrow F in FIG. 1).

Secondary air conduit 31 is generally L-shaped and runs longitudinallyfrom opening 30 in the rear 24 surface of the housing 18 to main passage26. One-way flow valve 50 is mounted to the inner surface 33 of the mainpassage 26 via a conventional spring-biased hinge mechanism (not shown),which is adapted to cause the valve 50 to completely block air flow Sthrough the conduit 31 to the main passage 26 when the pressure of theair flow F in the main passage 26 is below a predetermined thresholdindicative of inhalation through the passage 26 by a user.

Powder dispensing chamber 51 is formed in housing 18 for holding acapsule 34 containing the powder medication to be inhaled. Housing 18includes a moveable panel portion 32 in the rear 24 for permitting thecapsule 34 to be introduced into the chamber 51 and placed on a seat 52of vibratory element 36 between guiding means 60A, 60B. Preferably,element 36 comprises a hard plastic or metallic protective shell 37enclosing a piezoelectric vibrator (not shown). Preferably, thepiezoelectric vibrator is mechanically coupled to the drug cartridge 34so as to permit maximum vibratory energy to be transmitted from thevibrator to the cartridge 34. Guiding means 60A, 60B includes twosurfaces which slant downwardly toward the seat 52 so as to permit easyintroduction and retention of the capsule on the seat 52 in the chamber51. Removable panel 32 includes another air inlet 34 for permittingadditional air flow S2 from the chamber 51 through conduit 61 intoconduit 31 during inhalation by the user. Preferably, panel 32 andhousing 18 include conventional mating mounting means (not shown) forpermitting the panel 32 to be removably resecurable to the housing bythe user between introduction of fresh (i.e., completely full) capsulesand removal of spent (i.e., empty) capsules.

The piezoelectric element is made of a material that has ahigh-frequency, and preferably, ultrasonic resonant vibratory frequency(e.g., about 15 to 50 kHz), and is caused to vibrate with a particularfrequency and amplitude depending upon the frequency and/or amplitude ofexcitation electricity applied to the piezoelectric element. Examples ofmaterials that can be used to comprise the piezoelectric element includequartz and polycrystalline ceramic materials (e.g., barium titanate andlead zirconate titanate). Advantageously, by vibrating the piezoelectricelement at ultrasonic frequencies, the noise associated with vibratingthe piezoelectric element at lower (i.e., non-ultrasonic) frequenciescan be avoided.

In operation a drug-containing package 34 is punctured and inserted ontothe surface 52 of vibrator 36 in chamber 51 in the manner describedpreviously. The power switch is placed in the “ON” position and the userinhales air through the conduit 26, air flow F is generated throughconduit 26. This causes one-way valve 50 to deflect to admit air flow Sthrough opening 30 into conduit 26, and also causes air flow S2 throughopening 34 and chamber 51 into conduit 26. The inhalation of air streamF is sensed by a sensor 40 and is signaled to an actuation controller(not shown), which causes power to be supplied to a controller (notshown). The controller then adjusts the amplitude and frequency ofactuating power supplied to the piezoelectric element until they areoptimized for the best possible de-aggregation and suspension of thepowder P from the capsule into the air stream F via air flow S.

In a preferred embodiment of my aforesaid '809 and '146 patents, themedication or drug is supplied from a coiled tape having a plurality ofspaced blisters or wells for carrying controlled aliquots of a drypowder medication or drug.

BRIEF DESCRIPTION OF THE INVENTION

The present invention provides a dry powder inhaler which employssynthetic jetting technology to aerosolize drug powder from a blisterpack or the like. Synthetic jetting is not new. It was discovered atleast as early as 1950 that if one uses a chamber bounded on one end byan acoustic wave generating device and bounded on the other end by arigid wall with a small orifice, that when acoustic waves are emitted athigh enough frequency and amplitude from the generator, a jet of airthat emanates from the orifice outward from the chamber can be produced.See, for example, Ingard and Labate, Acoustic Circulation Effects andthe Nonlinear Impedance of Orifices, The Journal of the AcousticalSociety of America, March 1950. The jet, or so-called “synthetic jet”,is comprised of a train of vortical air puffs that are formed at theorifice at the generator's frequency. However, the use of a syntheticjet to deaggregate and eject a dry-powder material from a blister packor the like in a dry powder inhaler is new, and provides advantages overprior art dry powder inhalers.

More particularly, the present invention provides a dry powder inhalerhaving a first chamber for and holding a dry powder, and a secondchamber connected to the first chamber via a passageway for receiving anaerosolized form of the dry powder from the first chamber and fordelivering the aerosolized dry powder to a user. A vibrator is coupledto the dry powder in the first chamber. Since jetting efficiency fallsoff as the aspect ratio (length to cross-section or diameter) of thepassageway, in order to create a synthetic jet the passageway connectingthe first chamber to the second chamber preferably, but not necessarilyhas an aspect ratio equal to at least about one, and the vibrator isenergized and coupled to the first chamber so that the distance the gasmoves back and forth in the passageway is at least about twice thecross-section or diameter of the passageway.

In one embodiment of the invention, the first chamber is formed in theshape of a cylinder or blister with a vibratory element either formingone wall of the chamber, or the vibratory element is formed apart fromthe chamber and coupled to the blister.

In a second embodiment the first chamber is formed in the shape of ahorn, with a vibratory element either forming one wall of the chamber,or the vibratory element is coupled to a wall of the chamber via acolumn of gas.

In a third embodiment the first chamber is formed in the shape of ahorn, and a standing wave resonator is coupled to a wall of the chamber.

BRIEF DESCRIPTION OF THE DRAWINGS

Other features and advantages of the present invention will be seen fromthe following detailed description, taken in conjunction with theaccompanying drawings, wherein:

FIG. 1 is a perspective view of one embodiment of the inhaler of theprior art.

FIG. 2 is a diagram showing the interrelationship between a blistercontaining a medicament and the synthetic jet of the instant invention;

FIG. 3 is a cross-sectional schematic view of a chamber and vibratoryelement according to a first embodiment of the present invention;

FIG. 3 a is a cross-sectional view of an enlarged section of the elementof FIG. 3;

FIG. 3 b is a view similar to FIG. 3 a of an alternative embodiment of achamber element made in accordance with the present invention;

FIG. 4 is a cross-sectional schematic view of a chamber and vibratoryelement according to a second embodiment of the present invention;

FIG. 5 is a cross-sectional schematic view of a chamber and vibratoryelement according to a third embodiment of the present invention; and

FIGS. 6-9 are views similar to FIG. 5 of further embodiments of thepresent invention.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

Referring to FIG. 2, in bare essentials an inhaler 205 in accordancewith the present invention comprises a vibrator, e.g., a piezoelectricelement 204, a first chamber 203 and a second chamber 202 connected viaa passageway 201. The passageway 201 is sized and shaped such that areciprocating or oscillatory movement of the vibrator coupled to orforming a wall of the first chamber causes the gas in the first chamberto move back and forth through the passageway 201, such that essentiallythe same mass of gas is moved in each direction, while vortices of thegas are formed at the exits of the passageway 201 such that there is anet flow of gas away from the outlet end of passageway 201, i.e., asynthetic jet of gas is created by the vortices. A vibrator 204, whichis operatively connected either directly to the first chamber or via aclosed gas tube 206, creates vibrations in the chamber which generatethe synthetic jet at the outlet end of passageway 201. The dry powder210 in the chamber is levitated, at least partially deaggregated intoparticulate form within the first chamber 203, and suspended in the gasin the chamber to form an aerosol 212. The resulting aerosol is conveyedto the passageway 201 wherein at least a fraction of the suspended drypowder particles passes through the passageway 201 without returning tothe first chamber, thereby being communicated between the first chamber203 and the second chamber 202. The process continues until the majorityof the dry powder is evacuated from the first chamber 203.

Although synthetic jets can be formed outside of the bounds of thefollowing parameters, and thus are not excluded from the scope of thisinvention, the preferred parameters for forming the synthetic jets ofthis invention are as follows:

-   -   1. The aspect ratio of the passageway, i.e., the length to        cross-section or diameter of the passageway preferably is at        least 0.5 and preferably is greater than or equal to about one.        This aspect ratio helps ensure that the mass of gas that moves        back and forth in the passageway is created as discrete, well        formed slugs of air.    -   2. The distance the gas moves back and forth through the        passageway preferably is greater than about two times the        cross-section or diameter of the passageway. This ensures that        dry-powder disaggregated by the vortex created has a chance to        escape the vortex's presence before the gas moves back through        the passageway.    -   3. The turbulence associated with the vortices and reciprocating        gas within the chamber and passageway is minimized to enhance        the flow of the synthetic jet. Thus, the surfaces of the        passageway and the flange areas around the exits at both ends of        passageway 201 preferably will be made free of burrs and other        obstructions.    -   4. The passageway has a cross-section diameter in the range of        0.001″ to 0.050″.

To ensure the distance that the gas moves back and forth throughpassageway 201 is greater than about two times the cross-section ordiameter of the passageway 201, a minimum power density (or magnitude ofpressure change) should be present at the passageway 201. It is possibleto generate the minimum power density simply by causing a sufficientlyintense vibration in the first chamber 203. Optimally, the first chamber203 may include a resonator, e.g., a spring-mass or standing-waveresonator, and/or a horn that is used to concentrate energy near thepassageway and move the gas between the first chamber and the secondchamber.

As will be described below, in a preferred embodiment of the invention,the first chamber 203 and the passageway 201 comprise a pre-formedblister pack containing a dry powder medication or drug.

Referring to FIGS. 3 and 3 a, a blister pack 300 made in accordance witha preferred embodiment of the invention is formed from a tri-laminatematerial 305 comprising an oriented polyamide sheet 306 on the outside,a middle layer of aluminum foil 307, and polyvinylchloride sheet 308 onthe inside. The tri-laminate 305 is about 0.005″ thick, and is coldformed into a bowl-shaped base or bottom member 309 having a generallyflat bottom 310 of about 0.194″ diameter, an overall height of about0.270″ and a diameter at the widest point of about 0.350″.Alternatively, the blister pack may be formed with a flat bottom 320 asshown in FIG. 3 b. The bottom or base was partially filled with a drypowder, and a top 312, also formed of a tri-laminate was heat sealed tothe bottom. Four orifices 320 about 0.012″ diameter were formed in thetop of the blister with a spacing of about 0.056″ from the axis of thefirst chamber.

The bottom 310 of the blister pack 300 was placed in contact with aMurata MA40E7S piezoelectric transducer 314 (Murata Electronics NorthAmerica, Inc., Smyma, Ga.). About 0.006″ of the face 316 of thetransducer was removed in order to tune the piezo to a resonantfrequency of about 34 KHz. The transducer was driven at 34 KHz with avoltage of 150 Vpp. A standing wave resonator was created within theblister. Jets of up to 200 feet per minute were measured with a hot wireanemometer (VWR International catalog #21800-024), thereby producinggood evacuation and deaggregation of the dry powder from the blister.

FIG. 4 illustrates a second embodiment of the invention in whichacoustic horns are used to move the chamber gas from the first chamberto the second chamber. In the second embodiment, the powder dispensingchamber comprises a cylindrically-shaped first chamber 400 fabricatedout of a material such as polycarbonate. A vibratory element 408 isconnected to the proximal end of the first chamber 400 thereby causingthe magnitude of pressure variations communicated by the vibrator 408towards the distal end 410 of chamber 400. The resulting pressurevariations set up a synthetic jet which dispenses powder from firstchamber 400 into the second chamber 404 through passageway 412.

Several experimental cone-shaped horn profiles were machined out ofpolycarbonate to test the velocity of jets created by a horn-shapedfirst chamber. In a first example, shown in FIG. 5, the bottom 502 ofthe horn 504 had a diameter of about 0.400″ and was coupled to thevibrating surface 506 of a Murata MA40E7S piezoelectric transducer 508,from which material from the vibrating surface (the face) had beenremoved such that it had a resonance frequency of 30.4 KHz. Thevibrating surface of the transducer thereby formed the bottom wall ofthe first chamber. The length of the horn, i.e., from its bottom 502 tothe top 510 was 0.204″. The top end 510 of the horn had a diameter of0.1″. A piece of 0.0125″ thick polycarbonate shim stock 512 was adheredto the top of the horn. A orifice 514 of 0.012″ diameter was formed inthe shim stock such that it was approximately aligned with the axis 516of the horn. This configuration produced a standing wave resonance atapproximately 30 KHz. The transducer was driven at 29.8 KHz at 54 Vppand a corresponding jet velocity of 1030 feet per minute was measured atthe orifice 514. At a higher voltage of 120 Vpp a jet velocity of 1640feet per minute was measured. In both cases the jet velocity was higherthan necessary to achieve good evacuation and deaggregation of thepowder from the first chamber.

Referring to FIG. 6, another cone-shaped horn profile was machined outof aluminum. The bottom 602 of the horn had a diameter of about 0.400″and was coupled to the vibrating surface 604 of a Murata MA40E7Spiezoelectric transducer 606, from which material from the vibratingsurface (the face) had been removed such that it had a resonancefrequency of 30.4 KHz. Interposed between the vibrating surface 604 ofthe piezoelectric transducer and the horn was a thin laminate film 608comprising oriented polyamide on the outside, aluminum, andpolyvinylchloride on the inside, the film comprising an acoustic window.The tri-laminate was about 0.001″ thick and spaced about 0.01″ away fromthe vibrating surface of the piezoelectric transducer. As a result, thevibrations from the transducer were acoustically coupled to the insideof the horn. The distance between the top surface of film 606 and thebottom end of the horn 602 was 0.204″. The top end of the horn 602terminated in a wall 614 which was 0.010″ thick and in which were formed4 orifices 610 each of a diameter of 0.012″ with a spacing from the axis612 of the horn of 0.056″. A standing wave resonance frequency of 31.0KHz was produced. The transducer was driven at 31.0 KHz with a drivevoltage of 54 Vpp which produced a jet velocity of 434 feet per minute.When the drive voltage was increased to 120 Vpp the jet velocityincreased to 1381 feet per minute. In both cases, the jet velocity ismore than adequate to deaggregate and evacuate a dry powder from thechamber.

In a third embodiment of the invention, as shown in FIG. 7, a coneshaped first chamber 702 has a horn length (measured along its axis 704)of 0.204″. The configuration this provides simultaneously the benefitsof a standing wave resonator with the pressure magnitude amplificationof a horn to further reduce the magnitude of the pressure variationsrequired of the vibrator to create synthetic jets. In this embodiment,the vibrator 706 is operationally coupled to a flexible wall 710 of thefirst chamber 702, i.e., as shown in FIG. 7. Alternatively, as shown inFIG. 8, the vibrator 806 may be acoustically coupled to the firstchamber 808 through a gas tube 810, to an acoustic window 812, i.e., anarea of the first chamber 802 that is sufficiently thin and flexiblesuch that a majority of the vibrational energy will be transferred fromone side to the other side of the area. In this embodiment, it isadvantageous to minimize the gap between the vibrator 806 and theacoustic window 812 so that the spring constant presented by the mediumin the gas tube 812 is of the same order as that presented by theacoustic window 812. Thus, energy losses associated with the use of anacoustic window are minimized.

In a variant of the third embodiment, shown in FIG. 9, a wall 902 of thefirst chamber 904 may be formed by the vibrator, e.g., by making thewall of a polarized PVDF film, or the like and applying an alternatingvoltage across the PVDF film so that the PVDF film flexes and generatespressure waves.

Although cylindrical and cone shapes are described above, the chambersmay be made in a variety of shapes. In all cases one wall of the chambershould be flat or nearly flat or at least have a generally flattened orslightly rounded surface for interfacing or coupling with the vibratoryelement.

In each of the above described embodiments, in addition to the vibratorsmentioned, the vibratory elements may be a piezoelectric transducer, anelectrodynamic (loudspeakers) transducer or a magnetostrictivetransducer similar to those that are used in ultrasonic cleaning baths.It also is possible to employ a reciprocating piston pump to generateimpulses of gas that can induce synthetic jets. Any vibrator andconnection combination suitable for producing the vibrations necessaryfor generating synthetic jets is within the scope of the invention.

Other configurations are possible and yet are within the scope of thepresent invention. For example, it may be desirable to place an acousticwindow in the chamber to couple the energy from a transducer via a hornto the acoustic window of the chamber. This approach provides twoacoustic impedance transformations, one (the horn) which increases theacoustic pressure thereby matching the impedance provided at theacoustic window, and a second (the Helmholtz resonator) that matches theacoustic impedance of the air in the chamber.

Various additional changes may be made in the foregoing withoutdeparting from the spirit and scope of the invention, and will beapparent to those skilled in the art.

1-44. (canceled)
 45. A method of delivering a dry powder medication forinhalation therapy, comprising the steps of: providing a dry powderinhaler having a chamber for containing said dry powder; and coupling avibrator to said chamber to generate a synthetic jet stream comprising aseries of fluid vortices to propel said dry powder from said chamber.46. The method of claim 45, wherein the dry powder is delivered to thechamber in a closed packet.
 47. The method of claim 46, including thestep of piercing the pocket to release the dry powder.
 48. The method ofclaim 46, wherein the closed pocket comprises a blister pack.
 49. Themethod of claim 48, wherein the blister pack is constructed of metalfoil.
 50. The method of claim 48, wherein the blister pack isconstructed of a cold formed laminated material.
 51. The method of claim50, wherein the laminate material comprises a tri-HAYES laminate oforiented polyaminde, aluminum foil and polyvinylchloride.
 52. The methodof claim 48, wherein the blister pack is dome shaped.
 53. The method ofclaim 48, wherein the blister pack is cone shaped.
 54. The method ofclaim 46, wherein the vibrator comprises a piezoelectric transducer.